The objectives of this project are to examine the pharmacokinetics of nitroglycerin after oral and lung absorption. The particular emphases of study are the inter-relationships between plasma concentrations of intact nitroglycerin, oral bioavailability, intrinsic organic nitrate reductase activity, drug interaction and pharmacological effects. Nitroglycerin concentrations in plasma and selected tissues and organs will be determined by a gas chromatographic procedure previously developed in our laboratory. Rats will be given different diets (high carbohydrate, high protein, or high fat) and the bioavailability of oral nitroglycerin will be determined in these animals. The effect of age and diet on liver organic nitrate reductase activity will be examined. The possibility of drug interaction between nitroglycerin and other nitrates, and that between nitroglycerin and beta-adrenergic blocking agents such as propranolol will be investigated. These potential interactants were chosen for study because they have been reported either to be metabolized by liver organic nitrate reductase or to interfere with nitroglycerin metabolism in perfused liver systems. The relationship between lung absorption of nitroglycerin and the tolerance phenomenon it develops will be examined.